The previously established animal models for hepatic silicosis and fibrosis-associated carcinomas of the liver in nude-mice and hamsters (Williams and Knapton, Hepatology 1996;23:1268-75), obtained by treatment with crystalline silica (quartz) particles, were used for the following mechanism studies. The role of TGF-beta1 was investigated by immunohistochemistry, transmission and immune electron microscopy and by studies of TGF-beta1 mRNA expression, in hepatocytes and derived tumors. The immunolocalization of TGF-beta1 in mitochondria of murine liver and hearts was determined and its significance was investigated. Immunoelectron microscopic studies showed increased localization of TGF-beta1/latency-associated peptide in the mitochondria of mouse liver with quartz- induced fibrosis compared to controls. This finding provides evidence that TGF-beta1 may be involved in the mitochodrial respiratory chain of the liver cells following quartz-induced injury and fibrosis.